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Abstract Retinal degenerative diseases are a leading cause of vision loss and blindness globally, impacting millions. These diseases result from progressive damage to retinal pigment epithelial (RPE) cells for which no curative or palliative treatments exist. Cell therapy, particularly RPE transplantation, has emerged as a promising strategy for vision restoration. This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation. We discuss scaffold-free and scaffold-based approaches, including RPE cell suspensions and pre-organized RPE monolayers on biomaterial scaffolds. Key considerations, such as the form and preparation of RPE implants, delivery devices, strategies, and biodegradability of scaffolds, are examined. The article also explores the challenges and opportunities in RPE scaffold development, emphasising the crucial need for functional integration, immunomodulation, and long-term biocompatibility to ensure therapeutic efficacy. We also highlight ongoing efforts to optimise RPE transplantation methods and their potential to address retinal degenerative diseases.

One common cause of vision loss after retinal detachment surgery is retinal scarring. Here the authors demonstrate that a bio-functional polymer can prevent retinal scarring by suppression of epithelial-mesenchymal transition and hyper-proliferation of retinal pigment epithelial cells.

Simple Summary: This review serves as a comprehensive summary of how plaque radiotherapy, a specialized treatment for various eye tumors including uveal melanoma, is used to provide effective tumor control while preserving vision. The review discusses the radioisotopes available, explores various plaque designs, and describes clinical outcomes alongside possible complications. The review summarizes ongoing research and advancements that aim to enhance the effectiveness and safety of plaque brachytherapy, which is an important tool for the ocular oncologist. Plaque radiotherapy is an effective treatment modality for medium-sized ocular tumors such as uveal melanoma. The authors review the available literature and concisely summarize the current state of the art of ophthalmic plaque brachytherapy. The choice of radioisotope, which includes Ruthenium-106 and Iodine-125, depends on the intended treatment duration, tumor characteristics, and side effect profiles. Ophthalmic plaques may be customized to allow for the delivery of a precise radiation dose by adjusting seed placement and plaque shape to minimize collateral tissue radiation. High dose rate (HDR) brachytherapy, using beta (e.g., Yttrium-90) and photon-emitting sources (e.g., Ytterbium-169, Selenium-75), allows for rapid radiation dose delivery, which typically lasts minutes, compared to multiple days with low-dose plaque brachytherapy. The efficacy of Ruthenium-106 brachytherapy for uveal melanoma varies widely, with reported local control rates between 59.0% and 98.0%. Factors influencing outcomes include tumor size, thickness, anatomical location, and radiation dose at the tumor apex, with larger and thicker tumors potentially exhibiting poorer response and a higher rate of complications. Plaque brachytherapy is effective for selected tumors, particularly uveal melanoma, providing comparable survival rates to enucleation for medium-sized tumors. The complications of plaque brachytherapy are well described, and many of these are treatable. [ABSTRACT FROM AUTHOR]

Abstract Background Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs). Methods Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells. Results There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation. Conclusions These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials.

Introduction The aim of this study is to develop practical and affordable models to (a) diagnose people with diabetes and prediabetes and (b) identify those at risk of diabetes complications so that these models can be applied to the population in low-income and middle-income countries (LMIC) where laboratory tests are unaffordable.Methods and analysis This statistical and economic modelling study will be done on at least 48 000 prospectively recruited participants aged 40 years or above through community screening across 20 predefined regions in India. Each participant will be tested for capillary random blood glucose (RBG) and complete a detailed health-related questionnaire. People with known diabetes and all participants with predefined levels of RBG will undergo further tests, including point-of-care (POC) glycated haemoglobin (HbA1c), POC lipid profile and POC urine test for microalbuminuria, retinal photography using non-mydriatic hand-held retinal camera, visual acuity assessment in both eyes and complete quality of life questionnaires. The primary aim of the study is to develop a model and assess its diagnostic performance to predict HbA1c diagnosed diabetes from simple tests that can be applied in resource-limited settings; secondary outcomes include RBG cut-off for definition of prediabetes, diagnostic accuracy of cost-effective risk stratification models for diabetic retinopathy and models for identifying those at risk of complications of diabetes. Diagnostic accuracy inter-tests agreement, statistical and economic modelling will be performed, accounting for clustering effects.Ethics and dissemination The Indian Council of Medical Research/Health Ministry Screening Committee (HMSC/2018–0494 dated 17 December 2018 and institutional ethics committees of all the participating institutions approved the study. Results will be published in peer-reviewed journals and will be presented at national and international conferences.Trial registration number ISRCTN57962668 V1.0 24/09/2018.

Purpose. To identify systemic factors that may influence the response to anti-VEGF therapy in patients with diabetic macular edema (DME). Methods. 35 patients undergoing anti-VEGF injections for centre-involving DME were studied in this prospective observational study. The primary outcome was change in macular thickness one month after treatment, measured using spectral-domain optical coherence tomography (OCT). At baseline, information on various systemic factors was collected including glycosylated hemoglobin (HbA1c), serum VEGF levels, lipid profile and markers of renal function, and blood pressure. Thirty-three of the 35 patients were included in this study. Nonparametric statistical tests were used for the analysis of the data in view of the nonnormal distribution of the outcome variables. Multivariate analysis was performed using logistic regression. Stata 12.1 software was used for the analysis. Main Outcome Measures. Reduction in macular central subfield thickness (on spectral-domain OCT) and change in logMAR visual acuity at one month after injection. Results. Lower HbA1c levels (7% or less) were significantly associated with greater reduction in central macular subfield thickness at one month after injection of bevacizumab or ranibizumab on both univariate analysis (p=0.012) and multivariate analysis (p=0.042). Conclusions. Better glycemic control is associated with a greater reduction in central macular thickness after the first injection of bevacizumab or ranibizumab in diabetic macular edema. Patients with high levels of HbA1c and poor response to anti-VEGF may benefit from strict control of their blood glucose.

Acute retinal necrosis (ARN) following herpes simplex encephalitis (HSE) in an immunocompetent patient is a rare condition. Quantitative real-time polymerase chain reaction (qPCR) has made it possible to identify and quantify viral genome. We report a case of ARN following HSE managed with the help of qPCR. A 45-year-old man developed ARN following HSE and was treated with intravenous acyclovir and intravitreal foscarnet. The retinitis did not respond initially and the qPCR demonstrated a rise in the number of copies of the HSV-1 viral genome. With continued treatment with intravenous acyclovir and intravitreal ganciclovir, the retinitis healed and the qPCR confirmed a reduction in the viral load. qPCR has a high sensitivity and specificity for HSV and is a useful tool for diagnosis and treatment of viral retinitis.

The management of intra ocular tumors has undergone a sea change from the era of enucleation or external beam radiation. With the advent of new chemotherapy protocols, globe and vision salvage have become possible in a majority of cases of retinoblastoma. This article is an overview of the various modalities available for the management of intra ocular tumors and their indications. Chemotherapy has been covered elsewhere in this series of articles on ocular oncology. Photocoagulation and cryopexy are easily administered modalities of treatment for small tumors and totally within the ophthalmologist′s domain. Slightly larger tumors are treatable with brachytherapy. The susceptibility of the tumors to chemotherapy and radiation decide the choice of treatment and the dosage. Management of intra ocular tumors very often needs a multidisciplinary approach including ophthalmologist, oncologist, radiation physicist, and radiotherapist.

Background: Choroidal coloboma, especially with optic disc involvement affects the blood vessel (BV) pattern in the fundus. Aim: The aim of this study was to report the observations on the pattern of retinal BVs in eyes with fundus coloboma. Design: Retrospective observational study. Materials and Methods: Twenty four eyes of 19 patients with fundus coloboma and the disc involvement in the coloboma was classified according to a previous publication. Results: Four varieties of BVs were identified in the area of coloboma - BVs that were continuous with those arising from the optic disc; vessels emanating from the floor of coloboma whose continuity with central retinal artery or its branches could be indirectly established; and those emanating from the floor of coloboma whose continuity with central retinal artery could not be established. In addition, extraocular BVs were visible through the thinned sclera. The retinal BVs often traversed the coloboma to reach the normal retina. The disc itself was found to be small and had no physiological cup (if not colobomatous). Conclusions: One should be aware of the major BVs transgressing the coloboma while performing relaxing cuts in the intercalary membrane, during the surgery for retinal detachments in eyes with coloboma. Physiological cup is usually absent (when the disc is not colobomatous). Hence, any cupping in such eyes should be viewed with suspicion.

Choroidal neovascularization (CNV) is a rare complication associated with coloboma of the choroid. We describe three cases of coloboma choroid where there was loss of vision due to CNV development at the edge of the coloboma. One was managed by photodynamic therapy alone and two were managed by a combination of reduced fluence PDT and intravitreal bevacizumab. Significantly we noted that one treatment session was sufficient to achieve regression of the CNV and improvement in visual acuity.

Aim: To describe the clinical features, treatment and outcome patterns in 307 eyes with Coats′ disease. Materials and Methods: Retrospective chart review of patients diagnosed with Coats′ disease between January 1996 and January 2006 from a single referral center in southern India. Results: Two hundred and eighty patients (307 eyes) with mean age of 15.67 years (range: Four months-80 years) were included. Decreased vision (77%), unilateral affection (90%) and male preponderance (83.4%) were chief presenting features. Anterior segment involvement was seen in 67 (21.8%) eyes. Retinal telangiectasia were seen in 302 (99%) eyes, exudation in 274 (89%) eyes and retinal detachment in 158 (51.5%) eyes. Four-quadrant disease was seen in 207 (67.2 %) eyes. Visual acuity was < 20/200 in 249 (80.9%) eyes. One hundred and nine of 176 treated eyes (61.93%) had favorable anatomical outcome; 207 of 280 eyes (74%) had an optimal structural outcome. Seventeen (5.3%) eyes were enucleated. Complications following treatment included phthisis bulbi (7%), neovascular glaucoma (5%), epiretinal membrane (4.4%) and rubeosis iridis (4.4%). Conclusion: Indian patients with Coats′ disease have a high male predominance, the majority of whom present with severe visual impairment and extensive four-quadrant exudation. Unusual presentations such as pain, vitreous hemorrhage and a high incidence of anterior segment involvement are distinctive to Indian eyes.

Retinopathy of prematurity (ROP) is a significant cause of childhood blindness. The criteria for laser therapy have been revised from threshold ROP to include the earlier stage of high-risk prethreshold ROP. Laser photocoagulation is an established technique for the treatment of ROP. However, the detailed procedure and techniques for laser photocoagulation have not yet been published. Adequate and appropriate laser photocoagulation for ROP is different from the application of lasers in adult retinal vascular diseases, and many ophthalmologists need to be trained in this technique if the outreach of ROP treatment programs is to improve. Laser under topical anesthesia has been practiced in India as a preferred modality especially due to logistics and risks of general anesthesia in these pre-term babies. We discuss the details of the technique as practiced at tertiary care ophthalmic hospitals in India, so that the nuances in treatment parameters and clinical decision-making can be usefully applied to ophthalmic practice. This will ultimately lead to safe and effective treatment delivery in ROP.

Background: While lens-sacrificing vitrectomy is the standard approach to manage Stage 5 retinopathy of prematurity (ROP), scleral buckling has been used to manage some cases of Stage 4. Lens-sparing vitrectomy was popularized by Maguire and Trese in selected cases of Stage 4 disease. Purpose: To assess the functional and visual outcomes after primary lens-sparing pars plana vitrectomy for Stage 4 ROP. Materials and Methods: In a retrospective, interventional, consecutive case series, the records of 39 eyes of 31 patients presenting with Stage 4 retinal detachment secondary to ROP who underwent primary two or three-port lens-sparing vitrectomy from January 2000 to October 2006 were evaluated. The outcomes studied at the final follow-up visit were the retinal status, lens and medial clarity and visual acuity . Favorable anatomical outcome was defined as the retinal reattachment of the posterior pole at two months after the surgery; and favorable functional outcome was defined as a central, steady and maintained fixation, with the child following light. Results: At mean follow-up of 15 months, 74% of the eyes had a favorable anatomical outcome with single procedure. The visual status was favorable in 63% . The lens remained clear in all the eyes at the last follow-up, and the media clarity was maintained in 87%. Intraoperative complications included vitreous hemorrhage, pre-retinal hemorrhage and retinal break formation. Conclusions: Lens-sparing vitrectomy helps to achieve a favorable anatomical and functional outcome in selected cases of Stage 4 ROP.

Diabetic retinopathy (DR) at risk of vision loss (referable DR) needs to be identified by retinal screening and referred to an ophthalmologist. Existing automated algorithms have mostly been developed from images acquired with high cost mydriatic retinal cameras and cannot be applied in the settings used in most low- and middle-income countries. In this prospective multicentre study, we developed a deep learning system (DLS) that detects referable DR from retinal images acquired using handheld non-mydriatic fundus camera by non-technical field workers in 20 sites across India. Macula-centred and optic-disc-centred images from 16,247 eyes (9778 participants) were used to train and cross-validate the DLS and risk factor based logistic regression models. The DLS achieved an AUROC of 0.99 (1000 times bootstrapped 95% CI 0.98–0.99) using two-field retinal images, with 93.86 (91.34–96.08) sensitivity and 96.00 (94.68–98.09) specificity at the Youden's index operational point. With single field inputs, the DLS reached AUROC of 0.98 (0.98–0.98) for the macula field and 0.96 (0.95–0.98) for the optic-disc field. Intergrader performance was 90.01 (88.95–91.01) sensitivity and 96.09 (95.72–96.42) specificity. The image based DLS outperformed all risk factor-based models. This DLS demonstrated a clinically acceptable performance for the identification of referable DR despite challenging image capture conditions. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of transpupillary thermotherapy (TTT) in choroidal neovasularisation (CNVM) secondary to age related macular degeneration ( AMD). Material and methods: Retrospective, non-randomized study of 28 eyes of 28 patients with subfoveal CNVM (classic, occult or mixed) secondary to AMD. Results: Fifteen patients (53.57%) maintained their pre-treatment vision, 2 (7.14%) patients showed improvement of more than 2 lines and 11(39.28%) patients showed deterioration of vision by> 2 lines. Angiographic and clinical regression of CNVM was noted in 19 patients (67.8%) on an average follow up of 15.32 ± 3.31 months. Conclusion: TTT leads to stabilisation of vision in 60% of treated eyes with CNVM due to AMD.